The subject of the present invention is an improved process for the preparation of 2-halopyridine N-oxide.
2-Halopyridine N-oxides, especially 2-chloropyridine N-oxide, are important intermediate products for example in the preparation of pyrithiene, especially zinc pyrithione, which are effective as bactericides and fungicides.
Because of the electron-attracting properties of the halogens, 2-halopyridines can be oxidised with greater difficulty than other pyridine derivatives.
Therefore, there was first described the carrying out of the oxidation with peroxy acids whereby, however, the reaction is only incomplete and a multiple recycling of the unreacted starting material is necessary.
Furthermore, such peroxy acids are comparatively expensive and unstable (U.S. Pat. No. 2,951,844).
From U.S. Pat. No. 4,504,667, it is further known that 2-halopyridines can be reacted by means of peracetic acid with higher yields to give 2-halopyridine N-oxides when the peracetic acid is formed in situ from acetic acid and H2O2 in the presence of a catalyst. As catalyst, there are used maleic acid, maleic acid anhydride or phthalic acid anhydride in an amount of 0.1-0.8 mol/mol pyridine. A disadvantage of this process is that unreacted halopyridine must be laboriously removed, after neutralisation of the solution, by steam distillation and the added acetic acid and the catalyst remain in the aqueous phase as salts and thus are lost.
An improvement is described in U.S. Pat. No. 3,047,579, whereby 2-chloropyridine is reacted with hydrogen peroxide in the presence of pertungstic acid as catalyst. Here, too, the reaction with about 68%, with use of an excess of H2O2, is only incomplete, therefore requires a laborious working up and purification and especially a working up again of the expensive environmentally damaging heavy metal catalysts.
The U.S. Pat. No. 3,203,957 shows a further important advance, according to which the oxidation of 2-chloropyridine in an organic solvent is carried out with addition of aqueous 70% hydrogen peroxide and maleic acid anhydride. Conversions of over 50% are thereby achieved. A disadvantage of this process is that the maleic acid anhydride must be used in at least equimolar amount referred to the chloropyridine and thus large amounts of maleic acid are formed as waste products of the reaction which must be washed out from the reaction mixture with caustic soda solution and either disposed of as waste or can again be laboriously converted back into maleic acid anhydride. The separating off of the unreacted halopyridine after this process also makes difficulties.
Therefore, the task exists to find an improved process for the preparation of 2-halopyridine N-oxide, especially of 2-chloropyridine N-oxide, which can be carried out simply and economically.
The solution of this task is made possible by the features of the main claim and promoted by the features of the subsidiary claims.
Maleic acid anhydride and anthracene can be condensed (cf. O. Diels, K. Alder, xe2x80x9cAnnalen der Chemie, 486, pp. 191-202 (1931) and E. Clar, Annalen der Chemie, 486, 2194-2200 (1931)) in a Diels-Alder reaction to give a polycyclic compound (9,10-dihydro-9,10-ethane-anthracene-11,12-dicarboxylic acid anhydride) of the following formula I 
This condensation product reacts with H2O2 to give the peroxy acid of the formula II, 
which is able to oxidise 2-halopyridine to the N-oxide. Surprisingly, the acid thereby formed of the formula III 
under the reaction conditions, in spite of the water present in excess, is returned into the anhydride so that catalytic amounts of this compound suffice in order to make possible a complete reaction with the H2O2.
In contradistinction thereto, the reactions described in U.S. Pat. No. 3,203,957 require an at least equimolar amount of maleic acid anhydride or phthalic acid anhydride since, in the case of the reaction, the no longer catalytically acting maleic acid or phthalic acid is formed. In the case of the working up of the reaction batch, the small amounts of the catalyst of formula I remain preponderantly in the unreacted 2-halopyridine and can thus always again be returned into the reaction. A laborious purification and recovery of the catalyst is thereby unnecessary.
It is assumed that, instead of anthracene, other anthracene derivatives can also be used, such as the higher polycyclenes naphthacene or benz(a)anthracene, as well as the anthracenes substituted in the outer ring systems by alkyl or halogen which, in the same way, are still capable of a Diels-Alder reaction with maleic acid anhydride. These condensation products are, in the following, also to be regarded as being included by the designation anhydride I. It appears to be decisive that the reformation of the anhydride I from the acid is favoured via the steric fixing of the neighbouring carbon, whereby a use of merely catalytic amounts of this compound is possible and, on the other hand, the large aromatic radical brings about the solubility of this compound in the organic phase so that the catalyst compound remains behind in the case of the purification of 2-chloropyridine N-oxide. Less hindered Diels-Alder products, for example the cyclohexene-4,5-dicarboxylic acid anhydride formed from butadiene and MA or the cis-5-norbornene-endo-2,3-dicarboxylic acid anhydride formed with cyclopentadiene, appear not to be capable for the intermediate reformation of the anhydride since the reaction with hydrogen peroxide breaks off after consumption of the catalyst.
A preferred process variant consists in mixing 2-chloropyridine with catalytic amounts of the anhydride I, for example 1 to 25%, preferably 10 to 15%, and to add to this mixture, at temperatures between 50 and 100xc2x0 C., preferably about 70 to 80xc2x0 C., aqueous hydrogen peroxide with stirring. As hydrogen peroxide, there is used a commercially available 50 to 70% solution. After complete addition of the hydrogen peroxide, e.g. in a time of 0.5 h, in general it is kept further for about 1 to 3 h at the reaction temperature, thereafter cooled and the reaction phase extracted with water. The aqueous phase is worked up in per se known manner to 2-halopyridine N-oxide. The organic phase which, besides the unreacted halopyridine, contains small amounts of halopyridine N-oxide and the catalyst, is recycled into the next batch so that in this regard no losses occur. After the addition of fresh 2-halopyridine, this phase can be directly used again for subsequent reactions without further purification.
The reaction normally takes place without addition of solvents since the 2-chloropyridine sufficiently fulfils this purpose but an addition of an inert solvent is possible, for example of a chlorohydrocarbon, such as methylene chloride, of a paraffin hydrocarbon, such as cyclohexane or N-heptane, in order to dilute the reaction batch and, in the subsequent extraction with water, to promote the phase separation.
Since the catalyst is not hydrolysed with water, it is possible that the reaction mixture initially already contains water, for example from the preceding reaction cycle, whereby about 3-5% of water remain in the organic phase, or by direct addition of 3-20% of water. Otherwise, the water which is introduced with the hydrogen peroxide is dissolved in the warm reaction solution without formation of a second phase. An aqueous phase is first formed in the cold by addition of water, for example 25-100% of the mixture. Larger amounts are not useful since the working up costs increase, smaller amounts lead to a slower phase separation. Since the halopyridine N-oxide formed can be separated from unreacted halopyridine by extraction with water, in the sense of an economic reaction it is advantageous to work with an insufficiency of hydrogen peroxide. Hydrogen peroxide in an amount of 0.5 to one equivalent are thereby preferred. Since, as is known, in the case of the reaction, about 50% of the peroxide used is removed from the reaction via a breakdown into H2O and O2, only 20-50% of the chloropyridine used are reacted, the remainder remains behind as solvent for the catalyst (organic phase). On the other hand, the reaction can naturally also be controlled by addition of H2O2 in excess having regard to a substantially quantitative reaction. Depending thereon, high yields are obtained having regard to the peroxide used or to the pyridine derivative used.